The association of low serum alanine aminotransferase activity with mortality in the US population

Elevated alanine aminotransferase (ALT) activity, an important marker of liver injury, has been associated inconsistently with higher mortality. We evaluated whether persons with nonelevated ALT levels are the most appropriate comparison group by examining the relationships of low ALT with mortality and body composition in the US National Health and Nutrition Examination Survey (NHANES). In NHANES 1988-1994, the mortality risk of persons in ALT deciles 1, 2, 3, and 10 was compared with that of persons in deciles 4-9 (mortality was relatively flat across these deciles) over an 18-year period (through 2006) among 14,950 viral-hepatitis-negative adults. In NHANES 1999-2006, low ALT was evaluated in association with dual-energy x-ray absorptiometry body composition measures among 15,028 adults. Multivariate-adjusted mortality was higher for decile 1 (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.24, 1.63), decile 2 (HR = 1.27, 95% CI: 1.06, 1.53), and decile 3 (HR = 1.25, 95% CI: 1.04, 1.50) and nonsignificantly higher for decile 10 (HR = 1.21, 95% CI: 0.91, 1.61) than for deciles 4-9. Adjusted appendicular lean mass was decreased among the lowest ALT deciles. In the US population, low ALT was associated with higher mortality risk, possibly attributable to decreased appendicular lean mass. For mortality studies of elevated ALT levels, the most appropriate comparison group is persons in the middle range of ALT rather than all persons with nonelevated ALT.